Most of the recent approved therapeutic proteins are multi-subunit biologics, which need glycosylation and disulfide bridges for their correct conformation and biological functions. Currently, there exist many protein-based drugs that are mostly produced in the Chinese hamster ovary (CHO) cells. However, this expression system appears to associate with some limitations both in upstream and downstream processing steps, including low growth rate, sensitivity to different stresses and pathogens, and time-consuming purification processes. Some microalgae species offer a suitable expression system for the production of a wide range of recombinant proteins due to their key features such as fast-growing rate, having no common pathogens with the human, being used as the human food, and providing the possibility for the large-scale production in the closed/controlled bioreactors. More importantly, the protein biosynthesis machinery of some microalgae seems to be relatively similar to those of the human and animal cells. In fact, microalgae can assemble fully functional complex proteins that can be safely used in humans. In this review, we provide comprehensive insights into the currently used expression systems for the production of therapeutic proteins and discuss the essential features of the microalgae as a novel protein expression platform.